The overall goals of the program are to determine the factors contributing to the irreversible cerebral damage caused by various forms of hypoxia or ischemia and to apply this information to the clinical situation. In addition, a better understanding of the control of cerebral hemodynamics in the normal situation is being pursued. Various approaches to these problems are being utilized. On a basic level, animal models of stroke and shock are being studied. Regional cerebral blood flow and regional cerebral glucose metabolism as well as mitochondrial function, ion fluxes, tissue metabolites, cortical redox state, and ultrastuctural changes are being examined. In addition, the development of new methodology applicable to these problems is being pursued. On the clinical level, patients with cerebrovascular disease are being studied in an attempt to improve their prognosis. The intensive care and monitoring of patients with acute strokes is being undertaken to determine whether such as approach can favorably alter the outcome in these cases. The effect of mild elevation of blood pressure during the acute phase of stroke will be evaluated in a double blind randomized study. In addition, information concerning the usefulness of rCBF measurements and cognitive function studies in the evaluation of patients with acute strokes and T,I.A,'s will be obtained. Similar studies will be performed in patients undergoing carotid endarterectomy and microsurgical anastomosis. In the latter group cortical redox state will also be evaulated intraoperatively.